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Copper-mediated regulation of CK2 kinase activity
Thesis   Open access

Copper-mediated regulation of CK2 kinase activity

Alison Goupil
Master of Science (M.S.), Drexel University
Jul 2019
DOI:
https://doi.org/10.17918/gvse-ev81
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Abstract

Biology Protein kinase CK2 Oncology
The evolutionarily conserved serine/threonine kinase CK2 has hundreds of known substrates and plays an essential role in a number of signaling pathways that regulate cell growth and proliferation. Perturbances in these pathways are often associated with tumorigenesis, and indeed, overexpression of CK2 is associated with several cancer types and decreased patient survival. Compared to other protein kinases, CK2 displays several unusual properties, one being constitutive activity. Despite this apparent lack of regulation, it is hypothesized that some mode of regulation likely exists which is, as of yet, uncharacterized. In this study, we provide evidence that CK2 binds the transitional metal copper and that this binding is crucial for its kinase activity. Specific residues in the catalytic subunit of CK2 involved in copper-binding were identified and subsequently mutated. We demonstrate that this CK2 mutant has a decreased ability to phosphorylate substrate proteins in a glioblastoma cell line and in an in-vitro kinase assay. Overall, we provide preliminary data suggesting that CK2 kinase activity is regulated by its ability to bind copper. These results shed light on a novel mechanism controlling CK2 activity that may be important for targeting in cancers driven by CK2 kinase signaling.

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